1. Field of the Invention
This invention relates broadly to apparatus for collecting, processing and analyzing a liquid specimen. More particularly, this invention relates to an immunoassay apparatus and kit particularly useful for diagnosing disease.
2. State of the Art
Body fluid sampling and testing usually involves four steps: sample collection, extraction of the sample from the collection media, reaction of the sample with analytical reagents, and detection and/or measurement of physiologically active contents. The sampling of body fluids (e.g., blood), is typically accomplished in the field by trained personnel (e.g., nurses). The extraction of the sample, reaction of the sample with analytical reagents, and detection and/or measurement of contents has been traditionally performed in specialized laboratories by laboratory technicians. Recently, classical methods of analytical chemistry have been increasingly replaced by automated analyzers designed for the processing of well-defined specimens. These procedures are typically still conducted in highly specialized institutions by technicians trained in operating particular instruments. In addition, there has been an increasing recent trend to provide devices for the analysis of specimens in the field.
Several devices and methods have been described to collect liquid specimens by means of fibrous or other absorbent materials for subsequent processing and analysis. U.S. Pat. No. 4,409,988 to Greenspan teaches an apparatus for collecting cultures where the specimen is taken up by the absorbent tip of a swab which is then transferred into a culture medium. Similarly, U.S. Pat. No. 4,987,504 to Nason describes a specimen test unit for which the biological sample is also collected with a swab. For the collection of a specimen for medical diagnosis, EP 0 382 905 A2 to Schluter teaches the use of absorbent material for uptake of liquid and simultaneous separation of particulate matter. U.S. Pat. No. 4,635,488 to Kremer discloses a device with a nib containing porous material for absorption of a sample. A number of devices have been described for collecting oral fluid using an absorbent pad and extracting the fluid from the pad either with a barrel-piston arrangement—see, e.g., U.S. Pat. Nos. 4,418,702; 4,580,577; 4,774,962; 5,056,521, or by centrifugation—see, e.g., U.S. Pat. No. 4,774,962.
All of these applications teach the use of absorbent material to take up a liquid to be analyzed. However, each of these apparatus have certain limitations. In some cases, the absorbent material utilized has a large surface area which absorbs the sample and makes quantitative analysis difficult when the components to be analysed are in a low concentration. In other cases, the absorbent material can destroy or modify the molecules or components of the sample; e.g., via hemolysis of red blood cells in whole blood specimens, catalytic reactions, chemical reactions, etc.) In certain cases the provided absorbent material results in an inaccurate volume uptake, particularly in the situation of viscous liquids such as whole blood. In yet other cases, the absorbent material has a limited capacity for expression or desorption of the liquid taken up, so that it is difficult to recover small samples.
In an attempt to overcome these problems, U.S. Pat. No. 5,935,864 Schramm et al. which is hereby incorporated by reference herein in its entirety, provides a sample kit including a sample container with an open end and a capillary end and with a chamber disposed therebetween which includes an analytical testing strip. A reagent vial is provided with a penetrable foil seal. Liquid specimens are collected by bringing the capillary end of the sample container into contact with the liquid specimen to be analysed. The specimen is then tested by penetrating the foil seal of the reagent vial with the capillary end such that reagent is forced through the capillary end and into the chamber, thereby attempting to force contact of the sample with the analytical testing strip.
While the sample kit of Schramm et al. does overcome some of the problems of the prior art, it has its own problems. For example, the arrangement of using a reagent vial and forcing the reagent through the capillary end typically results in splashing within the chamber which results in some or all of sample not contacting the test strip. To overcome this problem, a splash filter has been utilized at the entrance of the capillary into the chamber. Another problem with the sample kit of Schramm et al. is the extremely limited amount of sample that is obtained by the capillary. Commercial product utilizing capillary action for sample take up collects approximately 3 microliters of blood. This amount of sample is not compatible with many test applications such as tuberculosis (TB) serology and TB antigen tests and other antigen detection systems which generally require larger sample volumes (e.g., 10-40 microliters). Further, problems arise with respect to the collection of blood with the Schramm et al. design because of the risk of an air bubble locating in the tip of the barrel which prevent capillary movement of the blood. Further yet, where a plasma or serum sample is to be analyzed, the sample should be provided to the capillary tip by a laboratory pipette, because the plasma or serum is often clear and successful capillary action is not readily evident to the naked eye. Dipping the barrel into the sample is not recommended because of air bubbles and the likelihood that there may not be enough back pressure to cause the sample to move up the capillary.